71. PREIMPLANTATION GENETIC DIAGNOSIS OF NEURODEGENERATIVE DISEASES. (August 2019) - Liao, C.H.
Abstract : Introduction: Preimplantation genetic diagnosis (PGD) has become a crucial approach to help carriers of inherited disorders give birth to healthy offspring. Here, we review the PGD methodologies and explore the use of polymerase chain reaction (PCR)-based technologies for PGD in neurodegenerative diseases that are clinically relevant and have typical features such as late-onset and severely debilitating. Material and Methods: Trophectoderm biopsies were performed at Day5/6 blastocyst stage. PGD using amplification refractory mutation system quantitative PCR (ARMS-qPCR) and/or linkage analysis was performed for 10 cases of various neurodegenerative diseases, underwent 13 oocyte retrieval cycles for in vitro fertilization (IVF) with PGD at the core laboratory of Dr. Ming Chen, a major PGD laboratory in Taiwan, during 2013-2016. Results: A total of 13 oocyte retrieval cycles were conducted. Among the 59 embryos analyzed, 49.2% (29/59) were unaffected and 50.8% (30/59) were affected. There were 12 embryo transfer cycles, of which 3 became pregnant and all pregnancies were delivered. The implantation rate and livebirth rate were 23.1% (3/13) per oocyte retrieval cycle and 25.0% (3/12) per embryo transfer cycle, respectively. Allele dropout (ADO) was noted in two embryos that were classified as unaffected by ARMS-qPCR but were evidenced as affected after prenatal diagnosis, rendering the false negative rate as 6.3% (2/32). Four among the 13 cycles underwent PGD by ARMS-qPCR coupled with linkage analysis and all of them were correctly diagnosed. Conclusions: PGD by PCR-based methods ( e.g., ARMS-qPCR and linkage analysis) is a feasible strategy whereas ADO is always a concern if ARMS-qPCR is used as the sole technology in PGD, especially in autosomal dominant diseases. Robust methodologies, proper genetic counseling that covers technical and ethical aspects of genetic testing, and confirmatory invasive prenatal diagnosis are important in PGD of neurodegenerative diseases.